Computational Studies of Au(I) and Au(III) Anticancer MetalLodrugs: A Survey

Owing to the growing hardware capabilities and the enhancing efficacy of computational methodologies, computational chemistry approaches have constantly become more important in the development of novel anticancer metallodrugs. Besides traditional Pt-based drugs, inorganic and organometallic complexes of other transition metals are showing increasing potential in the treatment of cancer. Among them, Au(I)- and Au(III)-based compounds are promising candidates due to the strong affinity of Au(I) cations to cysteine and selenocysteine side chains of the protein residues and to Au(III) complexes being more labile and prone to the reduction to either Au(I) or Au(0) in the physiological milieu. A correct prediction of metal complexes’ properties and of their bonding interactions with potential ligands requires QM computations, usually at the ab initio or DFT level. However, MM, MD, and docking approaches can also give useful information on their binding site on large biomolecular targets, such as proteins or DNA, provided a careful parametrization of the metal force field is employed. In this review, we provide an overview of the recent computational studies of Au(I) and Au(III) antitumor compounds and of their interactions with biomolecular targets, such as sulfur- and selenium-containing enzymes, like glutathione reductases, glutathione peroxidase, glutathione-S-transferase, cysteine protease, thioredoxin reductase and poly (ADP-ribose) polymerase 1.     

Solid-state 31P and 109Ag CP/MAS NMR as a powerful tool for studying of silver(I) complexes with N-thiophosphorylated thiourea and thioamide ligands

A family of three- and four-coordinated silver(I) complexes of formulas [Ag(PPh₃)₂L], [Ag(PPh₃)L], and [AgL]_n with N-thiophosphorylated thiourea and thioamide ligands of general formula RC(S)NHP(S)(OPri)₂ [R = Ph, PhNH, iPrNH, tBuNH, NH₂] have been studied by solid-state ¹⁰⁹Ag and ³¹P CPMAS NMR spectroscopy. ¹⁰⁹Ag NMR spectra have provided valuable structural information about Ag coordination, which is in good accordance with the available crystal structure data. The data presented in this work represent a significant addition to the available ¹⁰⁹Ag chemical shifts and chemical shifts anisotropies. The silver chemical shift ranges for different P,S-environments and coordination state were discussed in detail. The ¹J(³¹P–^107/109Ag) and ²J(³¹P–³¹P) values were determined and analyzed.     

Structure and emission properties of mixed-ligand Cu(I) complexes containing phosphinesulfide ligands

Mixed-ligand Cu(I) complexes containing phosphinesulfide ligands were synthesized, and the structure and emission properties were studied for the Cu(I) complexes. X-ray crystallographic study showed that a chelating phosphinesulfide and diimine are coordinated to Cu(I) center. Coordination geometry around Cu(I) center of each complex is described as a distorted tetrahedron. Some of the complexes show photoluminescence in the solid state.     

Four-coordinate N-heterocyclic carbene (NHC) copper(I) complexes with brightly luminescence properties

Three four-coordinate N-heterocyclic carbene (NHC) copper(I) complexes, [Cu(Py-Im)(POP)](PF₆) (P1), [Cu(Py-BenIm)(POP)](PF₆) (P2), and [Cu(Py-c-BenIm)(POP)](PF₆) (P3) (Py-Im = 3-methyl-1-(pyridin-2-yl)-1H-imidazolylidene, Py-BenIm = 3-methyl-1-(pyridin-2-yl)-1H-benzo[d]imidazolylidene, Py-c-BenIm = 3-methyl-1-(pyridin-2-ylmethyl)-1H-benzo[d]imidazolylidene, POP = bis([2-diphenylphosphino]-phenyl)ether), have been synthesized without transmetalation of the NHC–Ag(I) complex for the first time. The photophysical properties of the resultant NHC–Cu(I) complexes have been systematically investigated via spectroscopic methods. All complexes exhibit good photoluminescence properties with long excited-state lifetimes and moderate quantum yields. Density functional theory and time dependent density functional theory calculations were employed to rationalize the photophysical properties of the NHC–Cu(I) complexes.     

Polyethyleneimine Solubilized Luminescent Au(I)‐Thiolate Complexes for Highly Sensitive and Selective Cyanide Anion Sensing

Cyanide (CN^?) is a highly toxic anion to human beings, exploring efficient probes for sensitive and selective detection of it is very important. In this study, we explore a simple one‐pot reaction to synthesize polyethyleneimine (PEI) solubilized Au(I)‐MUA (11‐mercaptoundecanoic acid) complexes under mild condition. The as prepared Au(I)‐MUA complexes exhibit strong red photoluminescence (PL) and can act as sensitive and selective CN^? optical sensor in aqueous media based on the chemical reaction between CN^? and gold atom that quench the fluorescence, and the limit of detection is 10 nM, which is ～270 times lower than the maximum contamination level (2.7 μM) in drinking water permitted by WHO. Additionally, real water sample from a local lake is tested with these optical sensors, and the PL variation caused by 0.1 μ CN^? can be observed.     

Silver(I) and copper(I) complexes with ferrocenyl ligands bearing imidazole or pyridyl substituents

The reactions between five ferrocenyl derivatives containing both a CO and at least an imidazole or pyridine nitrogen atom and AgPF₆, AgOTf, or [Cu(NCCH₃)₄]PF₆ precursors were studied. The ligand {[bis(2-pyridyl)amino]carbonyl}ferrocene (L3), derived from (2-pyridyl)amine, favored tetrahedral coordination of Ag⁺ (with two ligands) and of Cu⁺ (with two acetonitrile ligands left from the precursor). In all the other ligands, both metal centers coordinated linearly to two ligands, preferring the imidazole or pyridinic nitrogen to other nitrogen atoms (amine) or oxygen donors.When the counter anions were triflate, the crystal structure showed a dimerization of the complex, with the ferrocenyl moieties occupying cis positions, by means of a weak Ag?Ag interaction. This was shown experimentally in the crystal structure of complex [Ag(L1)₂]OTf (L1 = ferrocenyl imidazole) and in the presence of peaks corresponding to {Ag₂(L2)₃(OTf)}⁺ and {Ag₂(L2)₄(OTf)}⁺ in the mass spectra of [Ag(L2)₂]OTf (L2 = ferrocenyl benzimidazole). In all complexes containing PF₆, there was no evidence for dimerization. Indeed, in the crystal structure of [Ag(L2)₂]PF₆, the ferrocenyl moieties occupy trans positions and the metal centers are far from each other. DFT calculations showed that the energy of the cis and trans conformers is practically the same and the balance of crystal packing forces leads to dimerization when triflate is present.     

Synthesis, characterization and luminescence properties of copper(I) complexes containing 2-phenyl-3-(benzylamino)-1,2-dihydroquinazolin-4(3H)-one and triphenylphosphine as ligands

Some copper(I) complexes of the formula [Cu(L)(PPh₃)₂]X (1-4) [where L = 2-phenyl-3-(benzylamino)-1,2-dihydroquinazolin-4(3H)-one; PPh₃ = triphenylphosphine; X = Cl⁻, NO₃⁻, ClO₄⁻ and BF₄⁻] have been prepared and characterized on the basis of elemental analysis, IR, UV-Vis and ¹H NMR spectral studies. The representative complex of the series 4 has been characterized by single crystal X-ray diffraction which reveal that in the complex the central copper(I) ion assumes the irregular distorted-tetrahedral geometry. Cyclic voltammetry of the complexes indicate a quasireversible redox behavior corresponding to Cu(II)/Cu(I) couple. All the complexes exhibit intraligand (π → π^∗) fluorescence with high quantum yield in dichloromethane solution.     

Cu(I) and Ag(I) complexes of chalcogenide derivatives of the organometallic ligand dppf and the dppa analogue

New Cu(I) and Ag(I) complexes were prepared by reaction of [M(NCCH₃)₄][X] (M = Cu or Ag; X = BF₄ or PF₆) with the bidentate chalcogenide ligands Ph₂P(E)NHP(E)Ph₂ (E = S, S₂dppa; E = Se, Se₂dppa), and dpspf (1,1′-bis(diphenylselenophosphoryl)ferrocene). Copper and silver behaved differently. While three molecules of either S₂dppa and Se₂dppa bind to a distorted tetrahedral Cu₄ cluster, with deprotonation of the ligand, 1:2 complexes of the neutral ligands are formed with Ag(I), with a tetrahedral coordination of the metal. The [Cu₄{Ph₂P(Se)NP(Se)Ph₂}₃]⁺ clusters assemble as dimers, held together by weak Se?Se distances interactions. Another dimer was observed for the [Ag(dpspf)]⁺ cation, with two short Ag?Se distances. DFT and MP2 calculations indicated the presence of attracting interactions, reflected in positive Mayer indices (MI). The electrochemistry study of this species showed that both oxidation and reduction took place at silver.     

Au(III) interaction with Methionine- and Histidine-containing peptides

Mononuclear Au(III) complexes of the peptides H-His-Met-OH (D) and H-Gly-Gly-Met-OH (T) and their N-protected forms Ac-His-Met-OH (Ac-D) and Ac-Gly-Gly-Met-OH (Ac-T) were structurally characterized by means of IR, MS and NMR. In the complexes with dipeptides [AuLCl₂]Cl (L = D or Ac-D), Au(III) is coordinated through S and imidazole N atoms from methionine and histidine fragments of the ligands forming macrochelate rings at mol ratio Au?:?L = 1?:?1. Additionally, Au(III) is coordinated by two terminal chloride ions in a square-planar arrangement. In complexes with the tripeptides [AuL′Cl] (L′ = T or Ac-T), however, the metal ion is coordinated in a tridentate fashion, through S and two N atoms, also at mol ratio M?:?L = 1?:?1. The fourth position of Au(III) is occupied by a Cl^? ligand.     

Three-ligand Co-assembled 2D Au(I)-Thiolate Nanosheets

Two-dimensional (2D) Au(I)-thiolate assemblies are a special type of material that can balance high structural stability and rich surface functionality, which shows promising prospects in both fundamental research and applications. Co-assembly of multiple ligands is a facile way to further enrich the surface properties and functions, and expand their application potentials. In this work, taking 3-mercaptopropionic acid (MPA), cysteine (Cys) and 1-thioglycerol (TGO) as example ligands, we studied in detail the possibility to co-assemble them into one nanosheet. Although the three ligands have significantly different controllability and pathways when self-assembling individually with Au(I), they can still be effectively co-assembled by reacting with HAuCl₄ together to obtain three-ligand nanosheets with good colloidal stability. The key points for successful co-assembly are also revealed by comparing single- and three-ligand self-assembly processes, laying a solid foundation for co-assembly of even more ligands. The easy but powerful strategy for 2D materials with closely-packed and multiple tunable surface functional groups addresses the surface engineering problem for 2D materials and paves the way for their wider applications in sensing and biomaterials.     

三价金配合物抗肿瘤活性研究*

三价金配合物具有潜在的抗肿瘤活性,是目前金属药物领域的研究热点。本文按配位原子的不同总结了稳定三价金配合物的结构特征,按其生物活性的构效关系、生物靶点和作用机制综述了三价金配合物抗肿瘤活性研究的最新成果：配体的结构特点以及离去基团对三价金配合物的体外细胞毒性影响较大;介绍了用于检测三价金配合物与可能的生物靶分子之间的相互作用的多种物理和生物学方法,重点关注了相互作用的模式,如嵌入/静电吸引/共价结合等,并解释了三价金配合物抗肿瘤活性的原因。最后提出了一些研究新思路,以期有助于设计得到靶标明确的具有良好药理活性的抗肿瘤药物。     

Pd(II) and Au(III) complexes of some 4-glycopyranosylamino-5-nitroso-6-oxo-pyrimidine derivatives

Six Pd(II) and Au(III) complexes of 4-glycopyranosylamino-5-nitroso-6-oxo-pyrimidine derivatives were prepared. On the basis of their¹H-NMR and IR spectra, it has been found that the coordination sites are the 5-nitroso and the 6-oxo substituents. Likewise, the thermal behaviour of the complexes has also been studied.

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Komplexe des Pd(II) und Au(III) mit einigen Derivaten des 4-Glycopyranosylamino-5-nitroso-6-oxo-pyrimidins

Zusammenfassung Sechs Pd(II)- und Au(III)-Komplexe mit 4-Glycopyranosylamino-5-nitroso-6-oxo-pyrimidin-Derivaten wurden hergestellt. Auf der Basis ihrer¹H-NMR und IR-Spektren wurde herausgefunden, daß die Substituenten 5-nitroso und 6-oxo die Koordinationsstellen sind. Das thermische Verhalten der Komplexe wurde ebenfalls untersucht.

     

Syntheses, structures and photochromism of two novel copper(II) complexes with 1,2-bis(2′-methyl-5′-(2″-pyridyl)-3′-thienyl)perfluorocyclopentene

Two novel Cu(II) complexes with 1,2-bis(2′-methyl-5′-(2″-pyridyl)-3′-thienyl)perfluorocyclopentene (BM-2-PTP) or its closed-form (closed-BM-2-PTP) were synthesized and characterized by X-ray crystallographic analysis. Both complexes are tetra-coordinated to two N atoms from distinct ligands and two Cl atoms from anions, forming 1-D polymeric structures. [Cu(BM-2-PTP)Cl₂] (1) showed typical spectral changes as analogous Ag(I) complexes with the same ligand upon appropriate light stimulus. However, closed-BM-2-PTP displayed different photocyclization from its open-ring form upon irradiation with UV light, indicating the photogenerated closed form turned into two kinds of closed-ring isomers. Furthermore, [Cu(closed-BM-2-PTP)Cl₂] (2) was revealed to contain two conformers by X-ray crystallographic analysis and displayed similarities in photocyclization to its free ligand. The distinct absorptions of the UV spectrum were attributed to the coexistence of two conformers in complex 2, both of which showed effective photoreactivities in the crystalline phase. The photochromic mechanism of complex 2 is tentatively concluded as two conformers displaying independent photoreactions.     

Electrochemical studies on the composition,stability constants and thermodynamics of TI(I) complexes with dithiodipropionic acid

The composition and stability constants of Tl(I) complexes with dithiodipropionic acid have been studied employingLingane's polarographic method,Calvin-Melchior'spH-metric technique, and conductance measurements. The thermodynamic functions G, H and S involved in complex formation are also determined at 30°C.

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Elektrochemische Untersuchungen von Zusammensetzung, Stabilitätskonstanten und Thermodynamic von Tl(I)-Komplexen mit Dithiodipropionsäure

Zusammenfassung Die Zusammensetzung und die Stabilitätskonstanten von Tl(I)-Komplexen mit Dithiodipropionsäure wurde mittels polarographischer Methoden (nachLingane),pH-metrischer Titration (nachCalvin-Melchior) und Leitfähigkeitsmessungen untersucht. Die thermodynamischen Funktionen der Komplexbildung (G, H und S) wurden bei 30°C bestimmt.

     

Au(Ⅰ)电荷转移配合物光谱性质的从头算研究

过渡金属电荷转移配合物的电荷分离是光能转化为电能的光物理过程, 与配合物的电子结构密切相关. 采用从头算方法探索了双核Au(Ⅰ)配合物, cis-[Au2(SHCH2PH2)2]2+(1), cis-[Au2(SHCH2S)2](2) 和cis-[Au2(PH2CH2S)2](3)的电荷转移性质. 采用MP2计算得到基态的Au(Ⅰ)—Au(Ⅰ)距离分别为0.2972, 0.2888和0.2903 nm, 表明Au(Ⅰ)之间存在弱吸引作用; 电子激发使得配合物2和3的金属间的距离缩短了约0.016 nm, 而配合物1仅增长了0.002 nm. CIS方法预测配合物1~3的3A激发态分别产生383, 463和422 nm最低能发射, 具有金属中心(Metal-centered, MC)跃迁和分子内电荷转移(Intramolecular Charge Transfer, ICT)的混合性质.     

Copper(I) and silver(I) complexes of bridging bis(quinaldinyl)phenylphosphine oxide ligand

Abstract

A novel tertiary phosphine oxide containing two quinaldinyl substituents has been synthesized according to adapted literature procedures. Its coordination properties toward Cu(I) and Ag(I) were investigated and the resulting complexes were analyzed by single crystal X-ray diffraction. Multinuclear complexes are formed, wherein the ligand is bridging across two metal centers. Though for the silver complex, no argentophilic interactions are present. The copper complex was characterized further by multinuclear NMR spectroscopy at variable temperatures.     

Ruthenium(II), copper(I) and silver(I) complexes of large bite bisphosphinite, bis(2-diphenylphosphinoxynaphthalen-1-yl)methane: Application of Ru(II) complexes towards the hydrogenation of styrene and phenylacetylene

Ruthenium(II), copper(I) and silver(I) complexes of large bite bisphosphinite Ph₂P{(-OC₁₀H₆)(μ-CH₂)(C₁₀H₆O-)}PPh₂ (1) are described. Reactions of bisphosphinite 1 with [Ru(η⁶-p-cymene)(μ-Cl)Cl]₂ and RuCl₂(PPh₃)₃ afford mono- and bis-chelate complexes [RuCl(η⁶-p-cymene){η²-Ph₂P{(-OC₁₀H₆)(μ-CH₂)(C₁₀H₆O-)}PPh₂-κP,κP}]Cl (2) and trans-[RuCl₂{η²-Ph₂P{(-OC₁₀H₆)(μ-CH₂)(C₁₀H₆O-)}PPh₂-κP,κP}₂] (3), respectively. Treatment of 1 with CuX (X = Cl, Br and I) furnish 10-membered chelate complexes of the type [Cu(X){η²-Ph₂P(-OC₁₀H₆)(μ-CH₂)(C₁₀H₆O-)PPh₂-κP,κP}] (4, X = Cl; 5, X = Br; 6, X = I), whereas [Cu(MeCN)₄]PF₆ affords a bis-chelated cationic complex [Cu{η²-Ph₂P(-OC₁₀H₆)(μ-CH₂)(C₁₀H₆O-)PPh₂-κP,κP}₂][PF₆] (7). Reaction between 1 and AgOTf produce both mono- and bis-chelated complexes [Ag{η²-Ph₂P(-OC₁₀H₆)(μ-CH₂)(C₁₀H₆O-)PPh₂-κP,κP}(SO₃CF₃)] (8) and [Ag{η²-Ph₂P(-OC₁₀H₆)(μ-CH₂)(C₁₀H₆O-)PPh₂-κP,κP}₂][SO₃CF₃] (9), respectively; whereas the similar reaction of 1 with[Ag(OTf)PPh₃] affords chelate complex of the type [Ag{η²-Ph₂P(-OC₁₀H₆)(μ-CH₂)(C₁₀H₆O-)PPh₂-κP,κP}(PPh₃)(SO₃CF₃)] (10). All the complexes were characterized by ¹H NMR, ³¹P NMR, elemental analysis and mass spectrometry, including low-temperature NMR studies in the case of silver complexes. The molecular structures of 4 and 6 are determined by X-ray diffraction studies. Ruthenium complexes 2 and 3 promote catalytic hydrogenation of styrene and phenylacetylene with good turnover numbers.     

A molecular mechanics force field for rhodium(I) carbonyl phosphine complexes and its application on the oxidative addition reactions of these complexes

The main purpose of the development of an Rh(I) Carbonyl Phosphine force field was to predict the molecular structure of Rh(I) complexes as well as to compute possible intermediates or transition states during the oxidative addition of CH₃I to these complexes. © 2000 John Wiley & Sons, Inc. J Comput Chem 21: 692–703, 2000     

(Phosphine)gold(I) Complexes of Benzenedithioles. Crystal structures of 1,2-benzenedithiolato-bis[triphenyl-phosphinegold(I)] and bis(triethylphosphine)gold(I) bis(1,2-benzenedithiolato)gold(III)

The reaction of 1,2- and 1,3-benzenedithiol C₆H₄(SH)₂ with chloro(phosphine)gold(I) complexes R₃PAuCl (R = Et, Ph) in the presence of triethylamine in tetrahydrofuran gives stable gold(I) complexes 1,2-C₆H₄(SAuPR₃)₂ [R = Et ( 1 ) and Ph ( 2 )] or 1,3-C₆H₄(SAuPPh₃)₂ ( 3 ), respectively, in high yield. The compounds have been characterized by analytical and NMR spectroscopic data. From the reaction of 1,2-C₆H(SH)₂ with Et₃P? AuCl a by-product [(Et₃P)₂Au]⁺ [Au(1,2? C₆H₄S₂)₂]^? ( 4 ) has also been isolated in low yield. The crystal structures of compounds 2 and 4 have been determined by single crystal X-ray diffraction. The gold(I) atoms in complex 2 are two-coordinate with bond angles S? Au? P of 175.2(1) and 159.5(1)°, Au? S bond distances of 2.304(1) and 2.321(1) å, and a short Au…?Au contact of 3.145(1) Å. The gold(I) atom in the cation of complex 4 is also linearly two-coordinate with a P? Au? P angle of 170.1(1) Å and Au? P distances of 2.296(3) and 2.298(3) Å. The geometry of the anion in 4 shows a square-planar coordination of gold(III) by two chelating 1,2-benzenedithiolate ligands with Au? S distances between 2.299(3) and 2.312(3) Å (for two crystallographically independent, centrosymmetrical anions in the unit cell).     

Achiral Au(I) Cyclic Trinuclear Complexes with High-Efficiency Circularly Polarized Near-Infrared TADF

Realizing high photoluminescence quantum yield (PLQY) in the near-infrared (NIR) region is challenging and valuable for luminescent material, especially for thermally activated delay fluorescence (TADF) material. In this work, we report two achiral cyclic trinuclear Au(I) complexes, Au₃(4-Clpyrazolate)₃ and Au₃(4-Brpyrazolate)₃ (denoted as Cl−Au and Br−Au) , obtained through the reaction of 4-chloro-1H-pyrazole and 4-bromo-1H-pyrazole with Au(I) salts, respectively. Both Cl−Au and Br−Au exhibit TADF with high PLQY (>70 %) in the NIR I (700–900 nm) (λ_max = 720 nm) region, exceeding other NIR−TADF emitters in the solid state. Photophysical experiments and theoretical calculations confirmed the efficient NIR−TADF properties of Cl−Au and Br−Au were attributed to the small energy gap ΔE_(S1-T2) (S = singlet, T = triplet) and the large spin-orbital coupling induced by ligand-to-metal-metal charge transfer of molecular aggregations. In addition, both complexes crystallize in the achiral Pna2₁ space group (mm2 point group) and are circularly polarized light (CPL) active with maxima luminescent dissymmetry factor |g_lum| of 3.4 × 10⁻³ ( Cl−Au ) and 2.7 × 10⁻³ ( Br−Au ) for their crystalline powder samples, respectively. By using Cl−Au as the emitting ink, 3D-printed luminescent logos are fabricated, which own anti-counterfeiting functions due to its CPL behavior dependent on the crystallinity.